Temporary Interruption of Treatment or Dose Modification of Ibrutinib in CLL Patients
A team from the Mayo Clinic in Rochester, USA, published a study this March in the journal Cancer Medicine, focusing on aspects of ibrutinib therapy in real clinical practice. The authors evaluated the impact of dose modification or temporary interruption of the drug administration.
Differences between Real Practice and Clinical Trials
Numerous clinical studies have demonstrated the efficacy of ibrutinib, the first BTK (Bruton's tyrosine kinase) inhibitor, in the treatment of patients with chronic lymphocytic leukemia (CLL). In clinical trials, adherence to treatment, the occurrence of adverse effects, and other parameters are carefully monitored. However, real-world clinical practice differs from clinical trials; many patients have comorbidities, concomitant medications, limited financial resources, or may forget to take their medications.
Studied Patient Population
The cited paper had a retrospective design and involved patients treated at the Mayo Clinic in Rochester, USA, between November 2013 and December 2017. Of the 209 patients, 74% had unmutated IGHV, 20% had TP53 alterations, and 22% were treatment-naive. Eighty-seven of these 209 patients started ibrutinib therapy at a reduced dose, i.e., < 420 mg/day. The reasons included physician choice, concomitant medications, etc. During the 281 patient-years of observed treatment, it was necessary to temporarily interrupt treatment in 91 out of 209 patients, primarily due to non-hematologic toxicity, surgical procedures, and less frequently due to hematologic toxicity or other reasons.
Findings
With a median follow-up of 24 months, the estimated median event-free survival (EFS) was 36 months; the median overall survival (OS) was not reached.
According to multivariable analysis, temporary interruption of ibrutinib administration (hazard ratio HR 2.37; p = 0.06) and TP53 alterations at the start of ibrutinib treatment (HR 1.81; p = 0.048) were associated with shorter EFS. Only TP53 alterations were associated with shorter overall survival (OS; HR 2.38; p = 0.015).
Conclusion
According to this study, the initial dose of ibrutinib or dose modification during treatment does not appear to influence EFS or OS parameters. However, temporary interruption of ibrutinib administration for any reason may be associated with shorter EFS and OS.
The results indicate that in real practice, more patients tend to discontinue ibrutinib treatment due to toxicity rather than disease progression. These findings need to be reflected in clinical practice, especially since it is a chronic oral medication.
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Source: Parikh S. A., Achenbach S. J., Call T. G. et al. The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice. Cancer Med 2020 May; 9 (10): 3390−3399, doi: 10.1002/cam4.2998.
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